Abstract

Population-based serum banks may allow for the early detection of shed markers of common gastrointestinal cancers. Few GI pan-biomarkers are available for serum testing and those that are lack specificity and universal sensitivity for colorectal, gastric and pancreatic cancers. The p87 antigen recognized by the Adnab-9 antibody may be an ideal candidate for such a biomarker. It has both diagnostic and prognostic biomarker ability for these GI cancers but its ability to detect the antigen in serum is unknown. Methods: In order to gauge feasibility of serum testing we conducted a literature search to determine the existence of model established serum banks internationally. An indirect Adnab-9 ELISA was performed on a validation set of sera from 20 CRC patients and 10 controls. A known positive stool extract was used as the positive control. Results: Six countries were found to possess serum banks with the numbers of specimens ranging from 1,982 to 2,132,215. Of these 6 countries, age-adjusted mortality from CRC was highest in the Netherlands at 21/100,000, from gastric cancer highest in Japan 35/100,000 and from pancreatic cancer highest in the USA 11/100,000. The validation sera set Australian patient demographics were similar for gender and ethnicity. The controls were significantly younger than the cancer patients (64±10.3 versus 52.2±3.4 years [p<0.002]) but there was no direct linear correlation between OD450 and age (r2=0.104;p=0.102). Dilution of serum at both 1:1 and 1:3 ratios showed significantly different mean OD450 values between cancer and control patients of 0.076±0.007 (x±STDEV) versus 0.069±0.006 (p<0.025) and 0.083±0.008 versus 0.074±0.004 (p<0.02) respectively. Eighty percent of cancer patients’ serum were positive versus 30% of controls (OR 9.3; CI 1.6-53.2;p<0.015). Signal to noise ratios of the positive control was satisfactory with the lowest OD450 reading at 0.085 obtained at a 1:6,400 dilution with a linear dilution-reaction curve. Conclusions: National serum banks already exist that could allow for graduated targeted screening of a specific disease based on relative mortality rates. The Adnab-9 antibody is a promising candidate for a pan-biomarker based on the outcome of the indirect ELISA. Since sensitivity of Adnab-9 stool binding is lowest for CRC compared to gastric and pancreatic, it is likely that serum testing for the other 2 cancers would yield comparable results. In order to elucidate this further, testing in prospective studies should be undertaken.